It is clear that certain environmental agents with little known toxicity of their own can greatly enhance the lethal and mutagenic action of other physical and chemical agents. An example of this is the effect of caffeine and related compounds on the lethal action of UV and X-irradiation and on the action of certain alkylating agents. Inhibition of purine biosynthesis has also been shown to cause serious damage, mainly embryotoxicity and teratogenicity. The interrelationship of these phenomena will be studied by examining the metabolism of caffeine in Chinese hamster ovary cells (CHO-Kl/pro-) and mutant cells defective in purine, pyrimidine, and amino acid metabolism grown in culture. Methods will include assessment of caffeine metabolism by high pressure liquid chromatography, the effect of caffeine on nucleotide biosynthesis, and the analysis of genetic repair processes in selected mutants under various experimental conditions.